CN112898366A - 16-dehydropregnene dienone alcohol acetate compound and preparation method thereof - Google Patents
16-dehydropregnene dienone alcohol acetate compound and preparation method thereof Download PDFInfo
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- CN112898366A CN112898366A CN202110041248.2A CN202110041248A CN112898366A CN 112898366 A CN112898366 A CN 112898366A CN 202110041248 A CN202110041248 A CN 202110041248A CN 112898366 A CN112898366 A CN 112898366A
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- -1 alcohol acetate compound Chemical class 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000001816 cooling Methods 0.000 claims abstract description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 30
- YLFRRPUBVUAHSR-UHFFFAOYSA-N 16-dehydro-pregnenolone Natural products C1C=C2CC(O)CCC2(C)C2C1C1CC=C(C(=O)C)C1(C)CC2 YLFRRPUBVUAHSR-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 10
- 150000004032 porphyrins Chemical class 0.000 claims abstract description 10
- 238000004440 column chromatography Methods 0.000 claims abstract description 5
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000000926 separation method Methods 0.000 claims abstract description 5
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000011347 resin Substances 0.000 claims description 35
- 229920005989 resin Polymers 0.000 claims description 35
- 235000019441 ethanol Nutrition 0.000 claims description 30
- 239000000047 product Substances 0.000 claims description 19
- 238000012544 monitoring process Methods 0.000 claims description 18
- 238000007539 photo-oxidation reaction Methods 0.000 claims description 18
- 239000012043 crude product Substances 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 15
- 238000001179 sorption measurement Methods 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 238000013375 chromatographic separation Methods 0.000 claims description 8
- UJKPHYRXOLRVJJ-MLSVHJFASA-N CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C Chemical group CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C UJKPHYRXOLRVJJ-MLSVHJFASA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 230000001276 controlling effect Effects 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 6
- 238000011010 flushing procedure Methods 0.000 claims description 6
- 229960003569 hematoporphyrin Drugs 0.000 claims description 6
- 239000012046 mixed solvent Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 239000003463 adsorbent Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 INLFWQCRAJUDCR-IQVMEADQSA-N 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000011068 loading method Methods 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical compound C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims 2
- 150000001242 acetic acid derivatives Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 abstract description 5
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- 230000015572 biosynthetic process Effects 0.000 abstract description 2
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- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 150000003431 steroids Chemical class 0.000 description 3
- MZWRIOUCMXPLKV-RFOVXIPZSA-N 16-Dehydropregnenolone acetate Chemical compound C([C@@H]12)C[C@]3(C)C(C(C)=O)=CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 MZWRIOUCMXPLKV-RFOVXIPZSA-N 0.000 description 2
- SCWLBXZTXMYTLF-UHFFFAOYSA-N cyclopropane-1,2-dicarbohydrazide Chemical compound NNC(=O)C1CC1C(=O)NN SCWLBXZTXMYTLF-UHFFFAOYSA-N 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 235000005903 Dioscorea Nutrition 0.000 description 1
- 241000234273 Dioscorea Species 0.000 description 1
- 235000000504 Dioscorea villosa Nutrition 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 235000004879 dioscorea Nutrition 0.000 description 1
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 238000004227 thermal cracking Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic photochemical synthesis, and discloses a 16-dehydropregnenolone alcohol acetate compound and a preparation method thereof, wherein the 16-dehydropregnenolone alcohol acetate compound comprises, by mass, 8-12 parts of pseudosteroid sapogenin, 35-50 parts of an organic solvent, 3-5 parts of a porphyrin photosensitizer and 10-20 parts of acetic acid. The invention prepares the 16-dehydropregnene dienol alcohol acetate compound by a photosensitive oxidation method, thereby eliminating the problem of environmental pollution from the source. Meanwhile, the constant-temperature cooling device is arranged outside the photochemical reactor, constant-temperature cooling is carried out in the reaction, the reaction is cooled to construct a constant-temperature reaction environment, and the cooling method can reduce water consumption and realize resource saving. The method performs column chromatography separation after preparation, has simple operation, good repeatability and high product purity, and is more suitable for industrial large-scale production.
Description
Technical Field
The invention belongs to the technical field of organic photochemical synthesis, and particularly relates to a 16-dehydropregnenolone alcohol acetate compound and a preparation method thereof.
Background
At present, steroid drugs are widely used in the fields of inflammation diminishing, allergy resisting, endocrine regulation, aging inhibition, contraception and the like, and the drugs are second only to antibiotics in the second major drug family. 16-Dehydropregnenolone acetate (16-Dehydropregnenolone acetate, 16-DPA) is the most important intermediate of steroid drugs, from which more than 70% of steroid drugs are produced. The 16-DPA is prepared by using diosgenin as a raw material and carrying out three reactions of thermal cracking, oxidation and elimination. At present, the oxidation reaction of the dioscorea pseudodiosgenin adopts a chromic anhydride oxidation technology at home and abroad, chromic anhydride belongs to a highly toxic and highly corrosive oxidant, and the use of the chromic anhydride causes serious environmental pollution due to the discharge of a large amount of chromium-containing solid waste and waste water. However, the existing method for preparing the 16-dehydropregnenolone alcohol acetate compound is complex in operation, serious in resource waste and high in energy consumption.
Through the above analysis, the problems and defects of the prior art are as follows: the existing method for preparing the 16-dehydropregnenolone alcohol acetate compound is complex in operation, serious in resource waste and high in energy consumption. The invention is completed under the subsidies of national natural fund (22061040) and Xinjiang Uygur autonomous region natural science fund (2020D01C 024).
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a 16-dehydropregnenolone alcohol acetate compound and a preparation method thereof.
The invention is realized in such a way that the preparation method of the 16-dehydropregnenolone alcohol acetate compound comprises the following steps:
setting the ambient temperature to be 23-26 ℃, keeping the air circulation degree at room temperature, adding pseudo-steroid sapogenins into a photochemical reactor, and then sequentially adding an organic solvent and a porphyrin photosensitizer into the photochemical reactor to obtain a mixed solvent;
introducing oxygen into the photochemical reactor, selecting a blue LED lamp with the wavelength of 380-600 nm as a reaction light source, and extending the reaction light source into the photochemical reactor; a constant temperature cooling device is arranged outside the photochemical reactor;
turning on a reaction light source to fully irradiate the mixed solvent in the photochemical reactor for 15-35 min to obtain a photo-oxidation product; starting the constant-temperature cooling device while starting the reaction light source, and driving water by using a motor through a driving module to complete water circulation;
fourthly, performing water circulation cooling by a circulation cooling module through a circulation cooling program, controlling each module to normally operate by a central control module through a main control computer, and monitoring the temperature of circulating water by a temperature monitoring module through a temperature sensor to obtain a temperature value of the water;
regulating the water temperature by a temperature regulating module by using a temperature regulating program; meanwhile, the display module is used for displaying the temperature value of the water in the water circulation by using the display to realize the cooling treatment of the photochemical reactor;
sixthly, collecting the photo-oxidation product, and distilling the photo-oxidation product under reduced pressure to remove the organic solvent in the photo-oxidation product to obtain a pure photo-oxidation product;
seventhly, placing the pure photo-oxidation product in a reflux device, adding acetic acid into the reflux device, and setting the reflux time to be 20-30 min for reflux; collecting reflux substances, carrying out reduced pressure distillation, and removing acetic acid to obtain a crude product;
step eight, macroporous adsorption resin pretreatment: soaking the macroporous adsorption resin in absolute ethyl alcohol for 24-48 h, then carrying out wet column packing with water, then flushing the resin column with absolute ethyl alcohol until the effluent liquid is added with distilled water with twice volume and does not generate turbidity, and then flushing the resin column with water until no alcohol smell is generated; then pouring out the resin in the column, and drying in vacuum at 15-35 ℃ to obtain the resin;
step nine, collecting the crude product, and selecting macroporous adsorption resin to carry out column chromatography separation on the crude product; the sample loading amount is 10ml per 100-200 ml of column volume, and the concentration of a crude product in the loaded solution is 3.5-4.5 mg/ml;
step ten, after chromatographic separation is finished, eluting with 10-50% by mass of ethanol water, wherein the amount of the eluent is 80-150 ml per 100-200 ml of column volume, and the elution flow rate is 2-3 ml/min; after the elution is finished, the 16-dehydropregnenolone alcohol acetate compound can be obtained.
Further, in the second step, the constant temperature cooling device is a water cooling device.
Further, in step two, the constant temperature cooling device includes: the device comprises a circulating cooling module, a driving module, a central control module, a temperature monitoring module, a temperature adjusting module and a display module;
the circulating cooling module is connected with the central control module and is used for carrying out water circulating cooling through a circulating cooling program;
the driving module is connected with the central control module and is used for driving water through the motor to complete water circulation;
the central control module is connected with the circulating cooling module, the driving module, the temperature monitoring module, the temperature adjusting module and the display module and is used for controlling the normal operation of each module through the main control computer;
the temperature monitoring module is connected with the central control module and is used for monitoring the temperature of the circulating water through the temperature sensor to obtain a temperature value of the water;
the temperature adjusting module is connected with the central control module and is used for adjusting the water temperature through a temperature adjusting program;
and the display module is connected with the central control module and is used for displaying the temperature value of the water in the water circulation through the display.
Further, in the fifth step, the adjusting the water temperature by the temperature adjusting module using the temperature adjusting program includes:
(1) acquiring first temperature value information of water in water circulation;
(2) judging whether the preset temperature is consistent with the first temperature numerical value information or not;
(3) when the preset temperature is inconsistent with the first temperature value information, adjusting according to the preset temperature and the first temperature value information;
(4) and when the preset temperature is consistent with the first temperature numerical value information, stopping adjusting.
Further, in the step (3), the adjusting uses a plate heat exchanger.
Further, in the eighth step, the macroporous adsorption resin is polar macroporous adsorption resin and/or non-polar macroporous adsorption resin.
Further, in the ninth step, the parameters of the macroporous adsorption resin are as follows: the particle size is 0.2-1.35 mm, the pore diameter is 12-35 nm, and the resin framework is polystyrene-divinylbenzene.
The invention also aims to provide a 16-dehydropregnenolone alcohol acetate compound prepared by the preparation method of the 16-dehydropregnenolone alcohol acetate compound, wherein the 16-dehydropregnenolone alcohol acetate compound comprises 8-12 parts of pseudosteroidal sapogenin, 35-50 parts of an organic solvent, 3-5 parts of a porphyrin photosensitizer and 10-20 parts of acetic acid in parts by mass.
Further, the organic solvent is one or a combination of ethyl acetate, benzene, dichloromethane, dichloroethane, acetonitrile and acetone.
Further, the porphyrin photosensitizer is one or a combination of more of hematoporphyrin, hematoporphyrin ether and meso-tetraphenylporphyrin.
By combining all the technical schemes, the invention has the advantages and positive effects that: the invention prepares the 16-dehydropregnene dienol alcohol acetate compound by a photosensitive oxidation method, thereby eliminating the problem of environmental pollution from the source. Meanwhile, the constant-temperature cooling device is arranged in the reaction process, the reaction is cooled to construct a constant-temperature reaction environment, and the cooling method can reduce water consumption and save resources. The method performs column chromatography separation after preparation, has simple operation, good repeatability and high product purity, and is more suitable for industrial large-scale production.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments of the present application will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained from the drawings without creative efforts.
FIG. 1 is a flow chart of a preparation method of 16-dehydropregnenolone alcohol acetate compounds provided by the embodiment of the invention.
Fig. 2 is a block diagram of a constant temperature cooling device according to an embodiment of the present invention.
FIG. 3 is a flow chart of a method for cooling a photochemical reactor provided by an embodiment of the present invention.
Fig. 4 is a flowchart of a method for adjusting water temperature by a temperature adjustment module using a temperature adjustment program according to an embodiment of the present invention.
FIG. 5 is a flow chart of a method for chromatographic separation of a crude product according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Aiming at the problems in the prior art, the invention provides a 16-dehydropregnenolone alcohol acetate compound and a preparation method thereof, and the invention is described in detail with reference to the accompanying drawings.
The 16-dehydropregnenolone alcohol acetate compound provided by the embodiment of the invention comprises, by mass, 8-12 parts of pseudosteroid sapogenin, 35-50 parts of an organic solvent, 3-5 parts of a porphyrin photosensitizer and 10-20 parts of acetic acid.
The organic solvent provided by the embodiment of the invention is one or a composition of more of ethyl acetate, benzene, dichloromethane, dichloroethane, acetonitrile and acetone.
The porphyrin photosensitizer provided by the embodiment of the invention is one or a composition of more of hematoporphyrin, hematoporphyrin ether and meso-tetraphenylporphyrin.
As shown in fig. 1, the preparation method of the 16-dehydropregnenolone alcohol acetate compound provided by the embodiment of the invention comprises the following steps:
s101, setting the ambient temperature to be 23-26 ℃, keeping the air circulation degree at room temperature, adding pseudosteroid sapogenins into a photochemical reactor, and then sequentially adding an organic solvent and a porphyrin photosensitizer into the photochemical reactor to obtain a mixed solvent;
s102, introducing oxygen into the photochemical reactor, selecting a blue LED lamp with the wavelength of 380-600 nm as a reaction light source, and extending the reaction light source into the photochemical reactor; a constant temperature cooling device is arranged outside the photochemical reactor;
s103, turning on a reaction light source to fully irradiate the mixed solvent in the photochemical reactor for 15-35 min to obtain a photo-oxidation product; starting a constant-temperature cooling device while starting a reaction light source to cool the photochemical reactor;
s104, collecting the photo-oxidation product, distilling the photo-oxidation product under reduced pressure, and removing the organic solvent in the photo-oxidation product to obtain a pure photo-oxidation product;
s105, placing the pure photo-oxidation product in a reflux device, adding acetic acid into the reflux device, and setting the reflux time to be 20-30 min for reflux; collecting reflux substances, carrying out reduced pressure distillation, and removing acetic acid to obtain a crude product;
s106, collecting a crude product, and carrying out chromatographic separation on the crude product; and eluting after chromatographic separation is finished to obtain the 16-dehydropregnenolone alcohol acetate compound.
In step S102, the constant temperature cooling device provided in the embodiment of the present invention is a water cooling device.
As shown in fig. 2, in step S102 provided in the embodiment of the present invention, the constant temperature cooling device includes: the device comprises a circulating cooling module 1, a driving module 2, a central control module 3, a temperature monitoring module 4, a temperature adjusting module 5 and a display module 6.
The circulating cooling module 1 is connected with the central control module 3 and is used for carrying out water circulating cooling through a circulating cooling program;
the driving module 2 is connected with the central control module 3 and used for driving water through a motor to complete water circulation;
the central control module 3 is connected with the circulating cooling module 1, the driving module 2, the temperature monitoring module 4, the temperature adjusting module 5 and the display module 6 and is used for controlling the normal operation of each module through a main control computer;
the temperature monitoring module 4 is connected with the central control module 3 and used for monitoring the temperature of the circulating water through a temperature sensor to obtain a temperature value of the water;
the temperature adjusting module 5 is connected with the central control module 3 and is used for adjusting the water temperature through a temperature adjusting program;
and the display module 6 is connected with the central control module 3 and is used for displaying the temperature value of the water in the water circulation through a display.
As shown in fig. 3, in step S103, the cooling of the photo-chemical reactor according to the embodiment of the present invention includes:
s201, starting a constant-temperature cooling device, and driving water by using a motor through a driving module to complete water circulation;
s202, performing water circulation cooling by a circulation cooling program through a circulation cooling module, and controlling each module to normally operate by a main control computer through a central control module;
s203, monitoring the temperature of the circulating water by using a temperature sensor through a temperature monitoring module to obtain a temperature value of the water;
and S204, adjusting the water temperature by using a temperature adjusting program through a temperature adjusting module, and displaying the temperature value of the water in the water circulation by using a display through a display module.
As shown in fig. 4, in step S205 provided by the embodiment of the present invention, the adjusting the water temperature by the temperature adjusting module using the temperature adjusting program includes:
s301, acquiring first temperature numerical value information of water in water circulation;
s302, judging whether the preset temperature is consistent with the first temperature numerical value information or not;
s303, when the preset temperature is inconsistent with the first temperature value information, adjusting according to the preset temperature and the first temperature value information;
s304, when the preset temperature is consistent with the first temperature numerical value information, stopping adjustment.
In step S303, a plate heat exchanger is used for the adjustment provided by the embodiment of the present invention.
As shown in fig. 5, in step S106 provided in the embodiment of the present invention, the crude product is subjected to chromatographic separation, which includes:
s401, collecting a crude product, and selecting macroporous adsorption resin for column chromatography separation;
s402, loading 10ml of sample per 100-200 ml of column volume, wherein the concentration of a crude product in a loaded solution is 3.5-4.5 mg/ml;
s403, after chromatographic separation is finished, eluting with 10-50% by mass of ethanol water, wherein the amount of the eluent is 80-150 ml per 100-200 ml of column volume, and the elution flow rate is 2-3 ml/min;
s404, after the elution is finished, the 16-dehydropregnenolone alcohol acetate compound can be obtained.
Before the chromatographic separation of the crude product, the embodiment of the invention also comprises the following steps: soaking the macroporous adsorption resin in absolute ethyl alcohol for 24-48 h, then carrying out wet column packing with water, then flushing the resin column with absolute ethyl alcohol until the effluent liquid is added with distilled water with twice volume and does not generate turbidity, and then flushing the resin column with water until no alcohol smell is generated; then pouring out the resin in the column, and drying in vacuum at 15-35 ℃ to obtain the resin;
in step S401 provided in the embodiment of the present invention, the macroporous adsorption resin is polar macroporous adsorption resin and/or nonpolar macroporous adsorption resin.
In step S401 provided in the embodiment of the present invention, the parameters of the macroporous adsorbent resin are: the particle size is 0.2-1.35 mm, the pore diameter is 12-35 nm, and the resin framework is polystyrene-divinylbenzene.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, and any modification, equivalent replacement, and improvement made by those skilled in the art within the technical scope of the present invention disclosed herein, which is within the spirit and principle of the present invention, should be covered by the present invention.
Claims (10)
1. A preparation method of 16-dehydropregnenolone alcohol acetate compounds is characterized by comprising the following steps:
setting the ambient temperature to be 23-26 ℃, keeping the air circulation degree at room temperature, adding pseudo-steroid sapogenins into a photochemical reactor, and then sequentially adding an organic solvent and a porphyrin photosensitizer into the photochemical reactor to obtain a mixed solvent;
introducing oxygen into the photochemical reactor, selecting a blue LED lamp with the wavelength of 380-600 nm as a reaction light source, and extending the reaction light source into the photochemical reactor; a constant temperature cooling device is arranged outside the photochemical reactor;
turning on a reaction light source to fully irradiate the mixed solvent in the photochemical reactor for 15-35 min to obtain a photo-oxidation product; starting the constant-temperature cooling device while starting the reaction light source, and driving water by using a motor through a driving module to complete water circulation;
fourthly, performing water circulation cooling by a circulation cooling module through a circulation cooling program, controlling each module to normally operate by a central control module through a main control computer, and monitoring the temperature of circulating water by a temperature monitoring module through a temperature sensor to obtain a temperature value of the water;
regulating the water temperature by a temperature regulating module by using a temperature regulating program; meanwhile, the display module is used for displaying the temperature value of the water in the water circulation by using the display to realize the cooling treatment of the photochemical reactor;
sixthly, collecting the photo-oxidation product, and distilling the photo-oxidation product under reduced pressure to remove the organic solvent in the photo-oxidation product to obtain a pure photo-oxidation product;
seventhly, placing the pure photo-oxidation product in a reflux device, adding acetic acid into the reflux device, and setting the reflux time to be 20-30 min for reflux; collecting reflux substances, carrying out reduced pressure distillation, and removing acetic acid to obtain a crude product;
step eight, macroporous adsorption resin pretreatment: soaking the macroporous adsorption resin in absolute ethyl alcohol for 24-48 h, then carrying out wet column packing with water, then flushing the resin column with absolute ethyl alcohol until the effluent liquid is added with distilled water with twice volume and does not generate turbidity, and then flushing the resin column with water until no alcohol smell is generated; then pouring out the resin in the column, and drying in vacuum at 15-35 ℃ to obtain the resin;
step nine, collecting the crude product, and selecting macroporous adsorption resin to carry out column chromatography separation on the crude product; the sample loading amount is 10ml per 100-200 ml of column volume, and the concentration of a crude product in the loaded solution is 3.5-4.5 mg/ml;
step ten, after chromatographic separation is finished, eluting with 10-50% by mass of ethanol water, wherein the amount of the eluent is 80-150 ml per 100-200 ml of column volume, and the elution flow rate is 2-3 ml/min; after the elution is finished, the 16-dehydropregnenolone alcohol acetate compound can be obtained.
2. The method for preparing 16-dehydropregnenolone alcohol acetate compounds according to claim 1, wherein in the second step, the constant temperature cooling device is a water cooling device.
3. The method for preparing 16-dehydropregnenolone alcohol acetate compounds according to claim 1, wherein in the second step, the constant temperature cooling device comprises: the device comprises a circulating cooling module, a driving module, a central control module, a temperature monitoring module, a temperature adjusting module and a display module;
the circulating cooling module is connected with the central control module and is used for carrying out water circulating cooling through a circulating cooling program;
the driving module is connected with the central control module and is used for driving water through the motor to complete water circulation;
the central control module is connected with the circulating cooling module, the driving module, the temperature monitoring module, the temperature adjusting module and the display module and is used for controlling the normal operation of each module through the main control computer;
the temperature monitoring module is connected with the central control module and is used for monitoring the temperature of the circulating water through the temperature sensor to obtain a temperature value of the water;
the temperature adjusting module is connected with the central control module and is used for adjusting the water temperature through a temperature adjusting program;
and the display module is connected with the central control module and is used for displaying the temperature value of the water in the water circulation through the display.
4. The method for preparing the dehydropregnenolone alcohol acetate compound according to claim 1, wherein in the step five, the adjusting of the water temperature by the temperature adjusting module by using a temperature adjusting program comprises the following steps:
(1) acquiring first temperature value information of water in water circulation;
(2) judging whether the preset temperature is consistent with the first temperature numerical value information or not;
(3) when the preset temperature is inconsistent with the first temperature value information, adjusting according to the preset temperature and the first temperature value information;
(4) and when the preset temperature is consistent with the first temperature numerical value information, stopping adjusting.
5. The method for producing 16-dehydropregnenediol acetate compounds according to claim 4, wherein in step (3), the adjustment is performed by using a plate heat exchanger.
6. The method for preparing 16-dehydropregnenolone alcohol acetate compounds according to claim 1, wherein in step eight, the macroporous adsorbent resin is polar macroporous adsorbent resin and/or non-polar macroporous adsorbent resin.
7. The method for preparing 16-dehydropregnenolone alcohol acetate compounds according to claim 1, wherein in the ninth step, the parameters of the macroporous adsorbent resin are as follows: the particle size is 0.2-1.35 mm, the pore diameter is 12-35 nm, and the resin framework is polystyrene-divinylbenzene.
8. The 16-dehydropregnenolone alcohol acetate compound is prepared by the preparation method of the 16-dehydropregnenolone alcohol acetate compound according to any one of claims 1 to 7, and is characterized in that the 16-dehydropregnenolone alcohol acetate compound comprises 8-12 parts by mass of pseudosteroidal sapogenin, 35-50 parts by mass of organic solvent, 3-5 parts by mass of porphyrin photosensitizer and 10-20 parts by mass of acetic acid.
9. The compound of claim 8, wherein the organic solvent is one or more selected from the group consisting of ethyl acetate, benzene, dichloromethane, dichloroethane, acetonitrile, and acetone.
10. The compound of claim 8, wherein the porphyrin photosensitizer is hematoporphyrin, hematoporphyrin ether or meso-tetraphenylporphyrin.
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